1. Field of the Invention (Technical Field)
The present invention relates to the field of full phase interferometry wherein the phase of the interferogram is recovered from only intensity measurements. Applications of the invention include phase-shifting interferometry, Fourier domain optical coherence tomography, and Fourier domain optical coherence reflectometry.
2. Description of Related Art
Note that the following discussion refers to a number of publications by author(s) and year of publication, and that due to recent publication dates certain publications are not to be considered as prior art vis-a-vis the present invention. Discussion of such publications herein is given for more complete background and is not to be construed as an admission that such publications are prior art for patentability determination purposes.
The ability to perform high resolution, subsurface imaging is needed in many fields including biology and medicine (tissue structure and pathology, cell morphology, tumor detection), materials science (composite, ceramic and microstructured materials characterization), and semiconductor device characterization. Application of optical techniques to biological materials is especially difficult because of the absorption and scattering characteristics of tissues. Several optical techniques that provide micrometer scale or better resolution have been applied to biological and medical imaging and each has different strengths and weaknesses. These techniques include confocal and two-photon fluorescence microscopy, confocal Raman spectroscopy, near-field optical microscopy, and optical coherence tomography (OCT), which is a term used for optical coherence reflectometry (OCR) when applied to biomedical imaging. Methods based on fluorescence or Raman scattering can provide high resolution and chemical specificity, but are not as useful for high resolution subsurface imaging because of absorption of either the input or signal wavelengths. On the other hand, OCT and other reflectometry techniques, such as spectral interferometry (SI), can provide structural information in scattering media at depths up to a few millimeters with a spatial resolution of a few micrometers. Imaging through centimeters of tissue can also be performed with reflectometry methods, but with much lower resolution. Since such methods detect reflective or back-scattering sites, they generally do not provide chemical identification. However, they are very useful for elucidating structure in heterogeneous or layered materials—such as skin tissue, for example. Furthermore, techniques like OCT and SI do not require fluorescence tagging, staining, or fixing of the sample.
The present invention is related to a rapid, high resolution optical imaging method and apparatus for, among other applications, clinical and biomedical research problems including studies of tissue response to drugs or radiation exposure, detection of cancerous and precancerous tissues, imaging of venous and arterial structures, and imaging of ocular pathologies. The method and apparatus, which will be referred to as complex differential spectral interferometry (CDSI), is based on the technique called differential spectral interferometry (DSI) described in U.S. Patent Application Publication No. 2004/0239946. The invention significantly improves the performance of DSI by allowing instantaneous acquisition of the full complex spectral interferogram and better resolving of the complex conjugate ambiguity, the major artifact problem of the DSI method. The CDSI method and apparatus can be easily used with fiber optics and can be incorporated into endoscopes, catheters and similar devices for in vivo applications.
Both CDSI and DSI are extensions of spectral interferometry (SI), a low coherence scattering technique, which performs measurements in Fourier domain (or frequency domain), as opposed to time-domain OCT (TD-OCT), which performs measurements in time domain. SI and TD-OCT are Fourier transform analogs. “Spectral interferometry” is also known as “Fourier domain Optical Coherence Tomography,” “frequency domain Optical Coherence Tomography,” “spectral domain Optical Coherence Tomography,” and “Spectral radar.” Both SI and TD-OCT have potential for imaging in tissue. Recent work has postulated that SI or Fourier domain OCT (FD-OCT) has the potential to have a large sensitivity advantage over conventional TD-OCT systems. Leitgib et al., Opt. Express 11, p. 889 (2003); Choma et al., Opt. Express 11, p. 2183 (2003); and de Boer et al., Opt. Lett. 28, p. 2067 (2003). However, this work also admits that the improvement in sensitivity is difficult to implement in practice. There are three reasons for the low sensitivity of conventional SI as compared to TD-OCT. First, SI is a DC measurement that causes large amounts of DC and 1/f noise to be integrated into the measured signal. Second, SI has background artifacts (so called autocorrelation terms) that cannot be removed by averaging. Third, SI images obtained from real-valued spectral interferograms suffer form the complex conjugate ambiguity (also known as reflection ambiguity or reflected image ambiguity), an artifact that is inherent to real Fourier transform. Because of this artifact, an SI image obtained from a real-valued interferogram consists of two overlapped images that are symmetrical with respect to the zero phase delay of the interferometer. To avoid ambiguity in interpretation of the image, the zero phase delay plane must be positioned outside of the imaged sample. Thus only one half of the imaging depth range is useful in practice.
An example of the “complex conjugate ambiguity” or “reflected image ambiguity” is shown schematically in FIG. 2. The figure depicts light being scattered from two surfaces of a thick, non-scattering object (glass plate, for example). The “center point” corresponding to zero phase delay of the interferometer is the center of the scan. In the case of TD-OCT, there is no reflection ambiguity about the center of the scan. In other words, the position of all scattering points relative to each other is preserved. In the case of SI, however, there appears to be two points on each side of the center scan. Worse, SI has a large DC background that is difficult to remove; it is a DC measurement with a large 1/f noise component. (The 1/f noise component can also contain sample movement and vibration-all low frequency noise sources.)
To remove the DC and autocorrelation artifacts, Applicants developed the DSI technique. Vakhtin et al., Opt. Lett. 28, p. 1332 (2003). DSI removes the DC component in SI measurements because lock-in or differential detection, phase-locked to a dither in the reference arm, passes detection frequencies only around the dither frequency. All frequencies at DC are removed where the majority of 1/f noise resides. (It should be noted, however, that the detection bandwidth can be quite small even though the detection frequency can be large.) The autocorrelation artifacts are also removed. Thus, DSI allows the greater dynamic range and sensitivity inherent in SI detection to be realized. DSI has additional advantages over conventional TD-OCT that result in a robust instrument suitable for research and clinical settings. These advantages include faster imaging rates and the simplification of the interferometer. However, the basic, single modulation version of DSI does not remove the complex conjugate artifact.
The problem of complex conjugate ambiguity has been addressed using different approaches, including phase-shifting methods, simultaneous detection of the quadrature components of the interferogram by using 3×3 fiber-optic couplers, and separation of the two complex conjugate images by choosing the appropriate carrier frequency in swept-source FD-OCT.
Phase-shifting methods allow acquisition of the complex spectral interferogram to be obtained in a multi-frame sequence. Schmitt and Creath, Appl. Opt. 34, p. 3610 (1995); and Wojtkowski et al., Opt. Lett 27, p. 1415 (2002). A multiple-phase-shift extension of DSI resolves the complex conjugate ambiguity. However, in practice the complex conjugate rejection ratio is limited by accuracy of the phase steps and also by the mechanical stability of the interferometer and the sample during the acquisition time of the frame sequence. Phase-shifting methods are sequential in nature and cannot provide simultaneous acquisition of the quadrature components of the complex spectral interferogram.
The detection of the complex interferogram using 3×3 fiber couplers as phase-shifting elements allows simultaneous detection of the real and imaginary components of the spectral interferogram. Choma et al., Opt. Left. 28, p. 2162 (2003); and Sarunic et al., Opt. Express 13, p. 957 (2005). This requires two separate detectors for acquiring the quadrature components. Slight misalignments in matching the spectrometers (in the case of broadband FD-OCT) and uneven wavelength-dependent splitting ratios in the coupler that lead to imperfect subtraction of the spectra (in the case of swept source FT-OCT) limit the suppression of the complex conjugate artifacts. The reported maximum complex conjugate rejection ratio is 20 dB for broadband FD-OCT and 25 dB for swept source FD-OCT. Sarunic et al., Opt. Express 13, p. 957 (2005).
Choosing the appropriate carrier frequency in swept-source FD-OCT separates the two mirror images and resolves the complex conjugate ambiguity. Zhang et al., Opt. Lett. 30, p. 147 (2005). However, this is not applicable to the parallel implementation of FD-OCT (which involves a broadband light source and detection of the spectral interferograms with an array detector). Also, when the full complex interferogram is not obtained, spectral information is lost.
The present invention, CDSI, improves DSI to better recover complex interferograms and resolve the complex conjugate ambiguity. Compared to other methods of full phase interferometry, the present invention provides a better complex conjugate rejection ratio and allows simultaneous acquisition of the quadrature components of the complex spectral interferogram.
The present CDSI invention has several important advantages over the current state of DSI including more accurate and instantaneous measurement of the complete complex interferogram with higher dynamic range than is possible using TD-OCT methods and possibility of combining spectral and structural imaging into one device. CDSI provides the potential for combining spectral and structure data. While some work has demonstrated that SI can provide some spectral information together with structural information, the best results have indicated that the full complex interferogram is required. Indeed, mathematically this is the case. Work with ultrashort laser pulse measurement (reconstruction of the pulse from spectrograms) indicates that full interferograms will be required to combine spectral and structural information in TD-OCT systems. Thus, only TD-OCT with complete digitization of the interferogram can provide both spectral and structural information together. Normally TD-OCT uses envelope detection which does not record much of the information required to obtain both spectral and structure information. Attempts to record the entire interferogram significantly reduce the dynamic range of the TD-OCT device. Morgner et al., Opt. Lett. 25, p. 111 (2000). In contrast, CDSI recovers the full complex interferogram, which provides the potential of combining both structural and spectroscopic imaging into one device without losing the dynamic range.